Paederus beetles

Fig. 18 Pederin and related compounds from Paederus beetles...

Piel J. A polyketide synthase-peptide synthetase gene cluster from an uncultured hacterial symbiont of Paederus beetles. Proc. Natl. Acad. Sci. U.S.A. 2002 99 14002-14007. 

The toxic effect of various species of rove beetles pertaining to the genus Paederus on the skin and eyes of mammals, including man, are due to the presence in their hemolymph of three vesicant amides pederin (104), pederone (105) and pseudopederin (106) (Fig. 18) [94,95], pederin being the major and most active of the three compounds. Their structure determination [96, 97] revealed rather unique substances until similar natural products with comparable biological activities were isolated from sponges of the genera Mycale [98,99], Stylinos [100] and Theonella [101-104]. 

Pederin (104), the powerful cytotoxin of staphylinid beetles of the genus Paederus, has been the object of renewed interest due to the unexpected discovery of a series of closely related compounds in marine sponges that display antitumor activities. The latter, as well as pederin, were prepared by total synthesis and their biological activities were reported [219,220]. A recent review summarizing present knowledge on this family of compounds has been published [221]. 

Pederin (735) is one of the most potent poisons known to man, with an LDso for rats of ca. 2 p.g per 100 g body weight. The pyran, which causes severe blistering of the skin, is part of the defence system of the beetle Paederus fuscipes. It inhibits chromosome division by first blocking protein synthesis and subsequently halting DNA synthesis. 

Figure 7 Pederin from a bacterial symbiont of Paederus and Paedericus spp. rove beetles.

Piel, J., Hofer, I., Hui, D. Evidence for a symbiosis island involved in horizontal acquisition of pederin biosynthetic capabilities by the bacterial symbiont of Paederus fuscipes beetles. J. Bacterial. 2004, 186, 1280-1286. 

Figure 22) is exemplary. First characterized from beetles of the genus Paederus the subsequent characterization of closely related structures such as theopederin A (67), isolated from a marine sponge fostered the speculation of a common bacterial source for this family of polyketides. " Subsequent studies by Kellner and Piel identified a bacterium from the genus Pseudomonas as the likely source of pederin. Natural product production by symbiotic bacteria has been reviewed by Piel (Chapter 2.14). 

Pederamide (12) is an important intermediate in the projected total synthesis of pederin (13), a component of the vesicant of the beetle Paederus fuscipes. /rart5-2-Butene epoxide has been converted (in 16 steps) into pederamide. One of these involved the conversion of the tetrahydrofuran (14) into the pyran-2-one (15) in 96% yield.Synthetic studies on lasalocid A (16) have continued with the use of carbohydrates as substrates for the construction of both furanoid and pyranoid rings of the antibiotic. ... 

C25H45NO9, Mr 503.63, mp. 113 C, LD50 (mouse i. v.) 2 ig/kg. Highly toxic amide from the hemolymph of the blister beetle Paederus fuscipes and related species. Contact with P. leads to severe skin diseases. P. and related compounds such as pederone (4 -Oxo-P.) inhibit the biosynthesis of proteins and mitosis and also have cytostatic activity. Similar compounds have been isolated from marine sponges ( mycalamides, onna-mides). ... 

Pederin (167) is a potent insect poison that is isolated from the East African beetle Paederus fuscipes. It is also a powerful inhibitor of the biosynthesis of proteins and of the mitosis of cells. The toxin has now been synthesized by... 

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